The Clinical Significance and Molecular Features of the Spatial Tumor Shapes in Breast Cancers

Abstract

Each breast cancer has its unique spatial shape, but the clinical importance and the underlying mechanism for the three-dimensional tumor shapes are mostly unknown. We collected the data on the three-dimensional tumor size and tumor volume data of invasive breast cancers from 2,250 patients who underwent surgery between Jan 2000 and Jul 2007. The degree of tumor eccentricity was estimated by using the difference between the spheroid tumor volume and ellipsoid tumor volume (spheroid-ellipsoid discrepancy, SED). In 41 patients, transcriptome and exome sequencing data obtained. Estimation of more accurate tumor burden by calculating ellipsoid tumor volumes did not improve the outcome prediction when compared to the traditional longest diameter measurement. However, the spatial tumor eccentricity, which was measured by SED, showed significant variation between the molecular subtypes of breast cancer. Additionally, the degree of tumor eccentricity was associated with well-known prognostic factors of breast cancer such as tumor size and lymph node metastasis. Transcriptome data from 41 patients showed significant association between MMP13 and spatial tumor shapes. Network analysis and analysis of TCGA gene expression data suggest that MMP13 is regulated by ERBB2 and S100A7A. The present study validates the usefulness of the current tumor size method in determining tumor stages. Furthermore, we show that the tumors with high eccentricity are more likely to have aggressive tumor characteristics. Genes involved in the extracellular matrix remodeling can be candidate regulators of the spatial tumor shapes in breast cancer.

Growth pattern can be used as a new characteristic to predict malignancy in breast cancer

“…More metastasis further indicates a worse prognosis. Consistent with our study, Han et al had shown that tumors with high eccentricity result in worse survival outcomes due to the high incidence of unfavorable prognostic factors, their results also showed that there was a significant association between the degree of eccentricity and the time to distant metastasis in patients with hormone receptor-negative tumors [7]. Our results showed that HR-positive tumors had a more spheroid shape than other subtypes, while the HER-2 status alone had no influence on the growth pattern.…”

“…Han's team had found that 54 genes were significantly correlated with tumor eccentricity in breast cancer. Among the genes with the highest p value, some genes related to extracellular matrix remodeling such as MMP13 and adamts12 were related to the tumors' growth pattern [7]. Besides, breast cancer lesions are not homogeneous.…”

Radiomic MRI Phenotyping of Glioblastoma: Improving Survival Prediction

“…Moreover, tumor enhancement on postcontrast T1-weighted images caused by blood-brain barrier disruption is associated with histopathologic tumor aggressiveness (29). As for tumor morphology, a previous study reported that breast tumors with high shape eccentricity were more likely to have aggressive characteristics (30). Consequently, radiomic features are composed of quantitative imaging characteristics, which are associated with tumor aggressiveness.…”

Computer-aided evaluation of the correlation between MRI morphology and immunohistochemical biomarkers or molecular subtypes in breast cancer

“…Moon et al . 23 measured the tumor volume and spheroid-ellipsoid discrepancy (CED) by the postoperative specimen. Tumor is nearly a round shape if SED measured closer to zero.…”